Neuroprotection by Mitochondrial NAD Against Glutamate-Induced Excitotoxicity.

Excitotoxicity is a pathological process that occurs in many neurological diseases, such as stroke or epilepsy, and is characterized by the extracellular accumulation of high concentrations of glutamate or other excitatory amino acids (EAAs). Nicotinamide adenine dinucleotide (NAD) depletion is an early event following excitotoxicity in many in vitro and in vivo excitotoxic-related models and contributes to the deregulation of energy homeostasis. However, the interplay between glutamate excitotoxicity and the NAD biosynthetic pathway is not fully understood.

An interactive dashboard for analyzing user interaction patterns in the i2b2 clinical data warehouse.

Background: Clinical data warehouses provide harmonized access to healthcare data for medical researchers. Informatics for Integrating Biology and the Bedside (i2b2) is a well-established open-source solution with the major benefit that data representations can be tailored to support specific use cases. These data representations can be defined and improved via an iterative approach together with domain experts and the medical researchers using the platform.

Rapid Deployment of a Pseudonymization Service in a Distributed Research Data Infrastructure - Lessons Learned.

The SARS-CoV-2 pandemic highlighted the importance of fast, collaborative research in biomedicine. Within the ORCHESTRA consortium, we rapidly deployed a pseudonymization service with minimal training and maintenance efforts under time-critical conditions to support a complex, multi-site research project. Over two years, the service was deployed in 13 sites across 11 countries to register more than 10,000 study participants and 15,000 biosamples.

Health Data Re-Identification: Assessing Adversaries and Potential Harms.

Sharing biomedical data for research can help to improve disease understanding and support the development of preventive, diagnostic, and therapeutic methods. However, it is vital to balance the amount of data shared and the sharing mechanism chosen with the privacy protection provided. This requires a detailed understanding of potential adversaries who might attempt to re-identify data and the consequences of their actions.

A Scalable Pseudonymization Tool for Rapid Deployment in Large Biomedical Research Networks: Development and Evaluation Study.

Background: The SARS-CoV-2 pandemic has demonstrated once again that rapid collaborative research is essential for the future of biomedicine. Large research networks are needed to collect, share, and reuse data and biosamples to generate collaborative evidence. However, setting up such networks is often complex and time-consuming, as common tools and policies are needed to ensure interoperability and the required flows of data and samples, especially for handling personal data and the associated data protection issues.

Molecular mechanisms of ischemia and glutamate excitotoxicity.

Excitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.

Proteostasis networks in aging: novel insights from text-mining approaches.

Aging is a topic of paramount importance in an increasingly elderly society and has been the focus of extensive research. Protein homeostasis (proteostasis) decline is a hallmark in aging and several age-related diseases, but which specific proteins and mechanisms are involved in proteostasis (de)regulation during the aging process remain largely unknown. Here, we used different text-mining tools complemented with protein-protein interaction data to address this complex topic.

Bacillary layer detachment in serpiginous-like choroiditis of presumed intraocular tuberculosis: Report of two cases.

Purpose: To describe the presence of bacillary layer detachment (BALAD) in serpiginous-like choroiditis (SLC) in presumed intraocular tuberculosis.

Observations: Clinical and multimodal imaging including fundus photography, fundus autofluorescence, and spectral domain and enhanced-deep imaging optical coherence tomography (OCT) of two cases of SLC in presumed intraocular tuberculosis. Two patients (26 and 38-year-old woman) presented with unilateral, decreased vision of acute onset.

The role of NAD metabolism in neuronal differentiation.

Background: Nicotinamide adenine dinucleotide (NAD) metabolism is involved in redox and non-redox reactions that regulate several processes including differentiation of cells of different origins. Here, the role of NAD metabolism in neuronal differentiation, which remains elusive so far, was investigated.

Material And Methods: A protein-protein interaction network between neurotrophin signaling and NAD metabolic pathways was built.

An International Comparison of Baseline Characteristics of Patients Undergoing Initiation of Anti-VEGF Therapy for DME.

Background And Objective: Diabetic macular edema (DME) is a leading cause of vision loss worldwide. The object of this study is to compare global differences of baseline characteristics of patients undergoing initiation of anti-vascular endothelial growth factor (VEGF) therapy for DME.

Patients And Methods: This multicenter, cross-sectional study included diabetic patients with foveal-involving retinal edema secondary to DME as documented by fundus exam and optical coherence tomography who were undergoing initiation of intravitreal anti-VEGF drugs.

Targeted O-glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced-stage bladder tumours.

Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short-chain O-glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST), which are generally associated with poor prognosis.

Ingestion of microplastics by commercial fish off the Portuguese coast.

The digestive tract contents of 263 individuals from 26 species of commercial fish were examined for microplastics. These were found in 17 species, corresponding to 19.8% of the fish of which 32.

Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics.

Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment.

Marine litter in bottom trawls off the Portuguese coast.

Benthic marine litter along the Portuguese coast, was recorded in 14 trips on stern trawlers covering a distance of 2117 km and an area of 56.2 km(2), average depth range 90-349 m. 2034 items of marine litter were registered, 76% were plastics and 38.

Cancer control capacity in 50 low- and middle-income countries.

Within the World Health Organization-International Atomic Energy Agency (WHO-IAEA) collaboration for delivery of technical assistance to its Member States, the National Cancer Control Programme/Plan (NCCP) Core Capacity Self-Assessment Tool has been used to obtain a simple and quick qualitative overview of national cancer control planning and on-going activities. The NCCP tool was applied in 50 Member States, which were classified as low- and middle-income countries in 2012. Results show that half of these countries reported having officially endorsed an NCCP and 42% were in the process of preparing or updating one.

High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas.

Sporadic medullary thyroid carcinoma (MTC) harbors RET gene somatic mutations in up to 50 % of cases, and RAS family gene mutations occur in about 10 %. A timely and comprehensive characterization of molecular alterations is needed to improve MTC diagnostic stratification and design-tailored therapeutic approaches. Twenty surgically resected sporadic MTCs, previously analyzed for RET mutations by Sanger sequencing using DNA from formalin-fixed paraffin-embedded samples, were investigated for intragenic mutations in 50 cancer-associated genes applying a multigene Ion AmpliSeq next-generation sequencing (NGS) technology.

Frequency of intestinal parasites in pet dogs from an urban area (Greater Oporto, northern Portugal).

The present study was conducted to evaluate the prevalence of gastrointestinal parasites in dogs with no clinical signs (n=175; group H) and in dogs with gastrointestinal disease (n=193; group D) that were admitted to a veterinary hospital. In group H, the overall prevalence of intestinal parasites (i.e.

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers.

Background: There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC).

Methods: HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes.

Results: Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations.

Tablet preformulations of indomethacin-loaded mesoporous silicon microparticles.

In this study, indomethacin-loaded thermally oxidized mesoporous silicon microparticles (TOPSi-IMC) were formulated into tablets with excipients in order to improve the dissolution and permeability properties of the poorly soluble drug. Formulations of TOPSi-IMC particles and excipients were prepared at different TOPSi-IMC particle ratios (25, 30 and 35%). The formulations were compressed by direct compression technique with a single punch tablet machine.